Genetic Variant HDAC3:p.Gln55Gln (chr5-141634927-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_003883.4(HDAC3):c.165A>G(p.Gln55Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 1,613,510 control chromosomes in the GnomAD database, including 308,611 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.67 ( 35290 hom., cov: 31)

Exomes 𝑓: 0.61 ( 273321 hom. )

Consequence

HDAC3
NM_003883.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.75

Variant links:

Genes affected

HDAC3 (HGNC:4854): (histone deacetylase 3) Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to the histone deacetylase/acuc/apha family. It has histone deacetylase activity and represses transcription when tethered to a promoter. It may participate in the regulation of transcription through its binding with the zinc-finger transcription factor YY1. This protein can also down-regulate p53 function and thus modulate cell growth and apoptosis. This gene is regarded as a potential tumor suppressor gene. [provided by RefSeq, Jul 2008]

HDAC3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP7

Synonymous conserved (PhyloP=1.75 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC3	NM_003883.4 link	c.165A>G	p.Gln55Gln	synonymous_variant	Exon 3 of 15	ENST00000305264.8	NP_003874.2	O15379-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC3	ENST00000305264.8 link	c.165A>G	p.Gln55Gln	synonymous_variant	Exon 3 of 15	1	NM_003883.4	ENSP00000302967.3		O15379-1

Frequencies

GnomAD3 genomes

AF:

0.670

AC:

101711

AN:

151868

Hom.:

35233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.847

Gnomad AMI

AF:

0.459

Gnomad AMR

AF:

0.694

Gnomad ASJ

AF:

0.570

Gnomad EAS

AF:

0.329

Gnomad SAS

AF:

0.641

Gnomad FIN

AF:

0.601

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.604

Gnomad OTH

AF:

0.659

GnomAD3 exomes

AF:

0.623

AC:

156603

AN:

251384

Hom.:

50727

AF XY:

0.617

AC XY:

83784

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.854

Gnomad AMR exome

AF:

0.767

Gnomad ASJ exome

AF:

0.562

Gnomad EAS exome

AF:

0.303

Gnomad SAS exome

AF:

0.656

Gnomad FIN exome

AF:

0.602

Gnomad NFE exome

AF:

0.599

Gnomad OTH exome

AF:

0.606

GnomAD4 exome

AF:

0.607

AC:

887792

AN:

1461524

Hom.:

273321

Cov.:

AF XY:

0.608

AC XY:

441945

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.852

Gnomad4 AMR exome

AF:

0.763

Gnomad4 ASJ exome

AF:

0.566

Gnomad4 EAS exome

AF:

0.343

Gnomad4 SAS exome

AF:

0.655

Gnomad4 FIN exome

AF:

0.603

Gnomad4 NFE exome

AF:

0.601

Gnomad4 OTH exome

AF:

0.605

GnomAD4 genome

AF:

0.670

AC:

101829

AN:

151986

Hom.:

35290

Cov.:

AF XY:

0.668

AC XY:

49614

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.847

Gnomad4 AMR

AF:

0.694

Gnomad4 ASJ

AF:

0.570

Gnomad4 EAS

AF:

0.329

Gnomad4 SAS

AF:

0.639

Gnomad4 FIN

AF:

0.601

Gnomad4 NFE

AF:

0.604

Gnomad4 OTH

AF:

0.660

Alfa

AF:

0.619

Hom.:

38073

Bravo

AF:

0.681

Asia WGS

AF:

0.575

AC:

2001

AN:

3478

EpiCase

AF:

0.589

EpiControl

AF:

0.587

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over